People in zero-gravity for prolonged periods are showing more medical issues .
https://www.space.com/23017-weightlessness.html
Long-term health effects
Astronauts  in space for weeks to months can run into trouble. Calcium in bones  secretes out through urine. As the bones weaken, astronauts are more  susceptible to breaking them if they slip and fall, just like people  with osteoporosis. Muscles also lose mass.
But time on the  International Space Station has helped NASA run studies on how astronaut  health is affected by time in weightlessness. Already the agency has  made changes. For example, it replaced the interim Resistive Exercise  Device (iRED) with the Advanced Resistive Exercise Device in 2008,  allowing astronauts to do weight-lifting without "maxing out" their top  weight. ARED is linked to better outcomes in bone density and muscle  strength, although all conclusions in space are hard to draw (in the  general since) since the astronaut population is fit already and  extremely small.
Astronauts typically have an allocated exercise  period of two hours a day in space to counteract these effects; this  time not only includes cardiovascular exercise and weight-lifting, but  also time to change clothes and set up or take down equipment. Despite  exercise, it still takes months of rehabilitation to adjust on Earth  after a typical six-month space mission. More recently, doctors have  discovered eye pressure changes in orbit. NASA has 
tracked vision changes in astronauts that were on the space station, but nothing so serious as to cause concern. Its cause is still under investigation, although one possible culprit includes 
spinal fluid that stays constant in microgravity  instead of the normal shifting that takes place on Earth as you lie  down or stand up. In addition to spinal fluid, a 2017 study tracked  changes in both short-flight and long-flight astronauts. Some studies  also point out that astronauts experience a slightly elevated level of  carbon dioxide on the station because of the filtration system; that gas  may also contribute to eye problems. 
Former NASA astronaut Scott  Kelly participated in a rare, one-year mission to the International  Space Station in 2015-16. His twin brother and former NASA astronaut  Mark (who retired before Scott) agreed to participate, along with Scott,  in several "twin experiments" to compare Scott's health in space with  that of Mark's on the ground. 
Preliminary results from one study released in October 2017 showed that different 
genes turn on or off in space. Other studies discussed earlier that year revealed 
subtle changes  as well. For example, telomeres (which slow down chromosome  deterioration) in Scott temporarily got longer in space. Scott also had a  slight deterioration in cognitive ability (thinking speed and accuracy)  and bone formation, although not enough to be concerning.
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Scientists  who work with microgravity health experiments note that often the  changes seen in orbit mimic what happens as people naturally age,  although often the processes are different. A group of Canadian  researchers — some of whom have expertise in space medicine — have  access to a long-term health facility for seniors at the University of  Waterloo. There, researchers can measure seniors in their residences  rather than bringing them into a lab, where the conditions are  artificial and can mask or exaggerate certain health conditions.
These may be real limitations to adapting people to long-term zero-G needed for Moon and Mars exploration
Not to mention the issues of radiation exposure.